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LC-MS bioanalysis of targeted nasal galantamine bound chitosan nanoparticles in rats’ brain homogenate and plasma

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Abstract

Validated LC-MS method for the direct quantitative analysis of galantamine (acetylcholinesterase inhibitor) was developed in rat cerebrospinal fluid and brain homogenate besides rat plasma, utilizing structurally close nalbuphine as an internal standard. After a simple protein precipitation step, samples are separated on 2-μm C18 column kept at 40 °C, using isocratic flow of 80% methanol in pH 9.5 ammonium formate buffer, and retention times were about 1.8 and 2.9 min for galantamine and nalbuphine, respectively. Mass detection with electrospray ionization (ESI) and positive polarity was able to detect 0.2 ng mL-1 galantamine using single ion monitoring mode (SIM) at m/z 288 for galantamine and m/z 358 for nalbuphine. The method showed linearity within the range of 0.5 – 300 ng mL-1. The proposed method was validated according to FDA guidelines. Trueness and precision showed acceptable values at all quality control levels, and recoveries were within 85.6 – 114.3% in all matrices at all runs and with relative standard deviations within 0.2 – 12.4%. The method was used to study in vivo brain uptake and pharmacokinetics of galantamine from brain homogenate and plasma samples following the administration of nasal galantamine-bound chitosan nanoparticles compared to oral and nasal galantamine solutions, in scopolamine-induced Alzheimer’s disease rat model.

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Abbreviations

GLA:

Galantamine

NLB:

Nalbuphine

CSF:

Cerebrospinal fluid

GLA-NP:

Nasal galantamine-bound chitosan nanoparticles

LLOQ:

Lower limit of quantification

LQC:

Low-quality control

MQC:

Medium-quality control

HQC:

High-quality control

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Acknowledgements

We would like to express our gratitude to Dr. Ragwa Farid, Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Pharos University in Alexandria, for her valuable contribution in the funding administrative support, and also to Dr. Amira Hanafy for providing pharmacokinetic analysis. We would like to thank Dr. Mennatallah A. Gowayed and Dr. Samar O. El-Ganainy for providing administration schedule and collection of biological samples.

Funding

This study was financially supported by the Academy of Scientific Research and Technology (ASRT), Egypt, under the ‘Egypt Knowledge and technology Alliances (EG-KTA) program’ (ID, KTA-C2-2.10).

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Authors and Affiliations

  1. Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Alexandria University, El-Messalah, Alexandria, 21521, Egypt

    Mahmoud Agami, Rasha A. Shaalan, Saied F. Belal & Marwa A.A. Ragab

  2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria, 21311, Egypt

    Rasha A. Shaalan

Authors
  1. Mahmoud Agami
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  2. Rasha A. Shaalan
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  4. Marwa A.A. Ragab
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Contributions

The authors alone are responsible for the content and writing of the manuscript. LC-MS method design and implementation: Mahmoud Agami. Writing, data interpretation, critical revision: Mahmoud Agami, Rasha Shaalan, Marwa Ragab. All the authors have given approval to the final version of the manuscript.

Corresponding author

Correspondence to Marwa A.A. Ragab.

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Conflict of interest

The authors report no competing interests.

Ethical approval for animal handling and their welfare

All animal studies in this project including their welfare adhered to the guidelines of the Research Ethical Committee of Faculty of Pharmacy, Pharos University in Alexandria, and complied to the “National Research Council’s Guide for the Care and Use of Laboratory Animals.” Approval No.: PUA01201903033001

Biological fluid source

The biological fluids were obtained from male Sprague Dawley rats (180–220 gm) in the animal house of Faculty of Pharmacy, Pharos University in Alexandria.

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Agami, M., Shaalan, R.A., Belal, S.F. et al. LC-MS bioanalysis of targeted nasal galantamine bound chitosan nanoparticles in rats’ brain homogenate and plasma. Anal Bioanal Chem 413, 5181–5191 (2021). https://doi.org/10.1007/s00216-021-03487-1

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  • DOI: https://doi.org/10.1007/s00216-021-03487-1

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